It is here proposed to study several critical differentiative processes associated with the development of Brugia malayi microfilariae. These studies are intended to generate new approaches for in vitro parasite cultivation, to further understanding of parasite interactions with host and vector, and to uncover new targets for drug or immune intervention in infection. The research focuses on three developmental processes involving microfilariae: the development and maintenance of sheath structure, the exsheathment process and its regulation, and the possible role of ecdysone-like hormones in the transition to subsequent larval stages. First, the possible role of chitin as a structural element in the microfilarial sheath will be examined using inhibitors of chitin synthesis. Induced morphological changes will be correlated with alterations in surface activities (antigenic and enzymatic) and microfilarial function (recirculation in the vertebrate and infection of the mosquito). Next, the process of exsheathment will be examined with respect to the signals which trigger it. Chemical and antibody-mediated methods of blocking exsheathment will be studied, and the effect of such blocking on filarial development in the vector will be examined. Finally, microfilariae will be analyzed for the presence of ecdysteroids. If such compounds can be detected, then differences in their levels will be sought in different developmental stages of the filarial life cycle. The possibility of interaction between worm-derived hormones and the insect vector will be tested, using modification of vector behavior during infection as a criterion. B. malayi was chosen for study because it is an agent of human lymphatic filariasis and because its complete life cycle can be readily maintained in the laboratory by passage between mosquito and a small rodent, the jird. This permits the study of developmental processes critical to transmission, and with immediate application to human infection and disease.